Msp1/ATAD1: mitochondrial and peroxisomal protein sorting

Msp1/ATAD1：线粒体和过氧化物酶体蛋白质分选

基本信息

批准号：
8988080
负责人：
Jared P Rutter
金额：
$ 26.15万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8988080
关键词：
ATP phosphohydrolase ATPase Domain Address Animal Model Biogenesis Brain C-terminal Cell model Cells Cellular biology Coupled Cultured Cells Cytosol Data Endoplasmic Reticulum Exhibits Failure Family Fibroblasts Gene Duplication Genome Goals Golgi Apparatus Heart Human In Vitro Maintenance Mammalian Cell Mammals Membrane Membrane Proteins Mitochondria Mitochondrial Proteins Modeling Morphology Mus Mutate Names Neurodegenerative Disorders Neuromuscular Diseases Organelles Outer Mitochondrial Membrane Pathology Patients Physiological Play Production Protein Overexpression Proteins Quality Control Respiratory physiology Role Signal Transduction Site Sorting - Cell Movement Stress System Tail Tissues Transmembrane Domain Vesicle Yeasts Zellweger Syndrome age related human disease mitochondrial dysfunction overexpression peroxisome protein expression protein transport public health relevance reconstitution respiratory response stressor trafficking

项目摘要

DESCRIPTION (provided by applicant): Mitochondria play a very important role in many aspects of cellular biology and mitochondrial dysfunction contributes to most age--‐related human diseases. As expected, there are a number of systems dedicated to maintaining mitochondrial function under stress. We recently identified an AAA ATPase that is required for the normal extraction of proteins that mislocalize to mitochondria, specifically those that have a single C--‐terminal transmembrane domain (tail--‐anchored). When this protein, named Msp1 in yeast and ATAD1 in mammals, is absent, cells exhibit progressive loss of mitochondrial respiratory function. The goals of this project are to: 1) define the mechanisms of substrate recognition and extraction using the yeast system; 2) determine whether ATAD1 is required for the maintenance of mitochondrial function in the mouse heart; 3) examine the impact of mitochondrial function on a patient with aberrant tail--‐anchored protein expression and a progressive neurodegenerative disease; 4) use Msp1/ATAD1 as a model protein by which to interrogate the mechanisms and importance of mitochondria--‐to--‐peroxisome vesicular trafficking; and 5) examine the role of Msp1/ATAD1 in limiting mitochondrial localization of peroxisomal proteins in conditions of impaired peroxisomal biogenesis, such as Zellweger syndrome.

描述（由适用提供）：线粒体在细胞生物学和线粒体功能障碍的许多方面起着非常重要的作用，这会导致大多数年龄 - 相关的人类疾病。如预期的那样，有许多系统致力于在压力下保持线粒体功能。我们最近确定了一种AAA ATPase，这是蛋白质正常提取到线粒体的正常提取所必需的，尤其是那些具有单个C ---末端跨膜结构域（尾巴锚定）的AAA ATPase。当这种蛋白质在酵母中称为MSP1和哺乳动物中的ATAD1时，细胞暴露于线粒体呼吸功能的进行性逐渐丧失。该项目的目标是：1）使用酵母系统定义底物识别和提取的机制； 2）确定在小鼠心脏中维持线粒体功能是否需要ATAD1； 3）检查线粒体功能对异常尾巴的患者的影响 - 锚定蛋白表达和进行性神经退行性疾病； 4）使用MSP1/ATAD1作为模型蛋白，通过该蛋白来询问线粒体的机制和重要性 - 至 - - 过氧化物酶体囊泡运输； 5）检查MSP1/ATAD1在限制过氧化物酶体生物发生的条件下（例如Zellweger综合征）中，过氧化物酶体蛋白的线粒体定位的作用。